SHIV-C109p5 NHP induces rapid disease progression in elderly macaques with extensive GI viral replication.

CCR5-tropic simian/human immunodeficiency viruses (SHIV) with clade C transmitted/founder envelopes represent a critical tool for the investigation of HIV experimental vaccines and microbicides in nonhuman primates, although many such isolates lead to spontaneous viral control post infection. Here, we generated a high-titer stock of pathogenic SHIV-C109p5 by serial passage in two rhesus macaques (RM) and tested its virulence in aged monkeys. The co-receptor usage was confirmed before infecting five geriatric rhesus macaques (four female and one male). Plasma viral loads were monitored by reverse transcriptase-quantitative PCR (RT-qPCR), cytokines by multiplex analysis, and biomarkers of gastrointestinal damage by enzyme-linked immunosorbent assay. Antibodies and cell-mediated responses were also measured. Viral dissemination into tissues was determined by RNAscope. Intravenous SHIV-C109p5 infection of aged RMs leads to high plasma viremia and rapid disease progression; rapid decrease in CD4+ T cells, CD4+CD8+ T cells, and plasmacytoid dendritic cells; and wasting necessitating euthanasia between 3 and 12 weeks post infection. Virus-specific cellular immune responses were detected only in the two monkeys that survived 4 weeks post infection. These were Gag-specific TNFα+CD8+, MIP1ß+CD4+, Env-specific IFN-γ+CD4+, and CD107a+ T cell responses. Four out of five monkeys had elevated intestinal fatty acid binding protein levels at the viral peak, while regenerating islet-derived protein 3α showed marked increases at later time points in the three animals surviving the longest, suggesting gut antimicrobial peptide production in response to microbial translocation post infection. Plasma levels of monocyte chemoattractant protein-1, interleukin-15, and interleukin-12/23 were also elevated. Viral replication in gut and secondary lymphoid tissues was extensive.IMPORTANCESimian/human immunodeficiency viruses (SHIV) are important reagents to study prevention of virus acquisition in nonhuman primate models of HIV infection, especially those representing transmitted/founder (T/F) viruses. However, many R5-tropic SHIV have limited fitness in vivo leading to many monkeys spontaneously controlling the virus post acute infection. Here, we report the generation of a pathogenic SHIV clade C T/F stock by in vivo passage leading to sustained viral load set points, a necessity to study pathogenicity. Unexpectedly, administration of this SHIV to elderly rhesus macaques led to extensive viral replication and fast disease progression, despite maintenance of a strict R5 tropism. Such age-dependent rapid disease progression had previously been reported for simian immunodeficiency virus but not for R5-tropic SHIV infections.

Efeitos dasMedidas restritivas de combate à covid-19 no cumprimento das rotinas de tratamento do hiv no centro de saúde de moamba / Effects of restrictive measures to combat covid-19 on compliance with hiv treatment routines at the moamba health center

Em países economicamente fragilizados, com alta prevalência de infecções por vírus de imunodeficiência humana, as medidas de saúde pública e administrativas adoptadas para prevenir, controlar e conter a propagação da pandemia da COVID-19 representaram ameaça às actividades de controlo e manejo do HIV. Objectivo: analisar os efeitos das medidas de prevenção, controlo e contenção da propagação da COVID-19 na adesão às rotinas de tratamento anti-retroviral entre pacientes atendidos no Centro de Saúde de Moamba. Métodos: Foi adoptada uma metodologia mista, de orientação quantitativa, para uma abordagem retrospectiva dos efeitos das medidas de controlo e contenção do coronavírus, entre 1 de Outubro de 2019 e 31 de Março de 2021. Para o efeito, foram escrutinados 20 processos clínicos (Fichas Resumo) de pacientes seguidos nos cuidados de HIV entre Outubro e Dezembro de 2018. Os titulares destas Fichas Resumo foram submetidos a entrevistas semiestruturadas (auto-relato) para identificar os factores que durante o período de vigência das Medidas restritivas de combate à COVID-19 afectaram o cumprimento das rotinas de tratamento anti-retroviral (comparecimento às consultas e adesão às datas de colecta de medicamentos). Os dados obtidos dos processos clínicos foram submetidos à análise estatística descritiva. O teste paramétrico do qui-quadrado (X2 ) foi utilizado para investigar associações e correlações entre as variáveis socioeconómica e biomédica. A informação obtida, por meio de entrevistas semiestruturadas (auto-relato), foi submetida à análise temática de Braun e Clark Resultados: Os achados do estudo mostram uma tendência de variação para o período anterior (aos 6meses) e posterior (12 e 18 meses) a introdução das medidas vigilância activa da COVID 19. Em relação à taxa de adesão estimada, a média achada para os 18meses estudados, foi de 96,22% (±3,38) e a mediana de adesão foi de 97,55% (IQR: 93.73% ­ 99,35%). Porém, aos 6meses de avaliação, foi de 97% (±2,04, intervalo de 92% a 100%), aos 12 meses atingiu 94,39% (±3,43%, intervalo 86%-98.9%) e estabilizou-se nos 96,6% (±2,72), aos 18 meses de avaliação. Quanto à média de dias de atraso no levantamento de medicamentos, a média achada para o período estudado foi de 3,3 dias (±1,72, IQR 2 ­ 4,75). Aos 6 meses de avaliação, a média de dia de atrasos foi de 0,5 dias (±0,61 IQR 0-1), aos 12 meses regrediu para 1,6 dias (±1,1 IQR: 1-3) e atingiu 1,2 dias (±0,89 IQR: 1-3) aos 18 meses de avaliação. A média de células CD4 achada nos pacientes foi de 455,12 células/mm³ (± 135,78, IQR: 345,3 células/mm³ ­ 585,03 células/mm³) para o período em estudo. Neste período, 40% (8/20) dos pacientes apresentaram CD4 inferior a 350 células/mm³; 60% (12/20) tinham CD4 superior a 350 células/mm³. A média de células CD4 por 1 mm³ de sangue foi de 72,8 células/mm³ (±156,27 células/mm³, IQR 342 células/mm³ e 594 células/mm³) aos 6 meses de estudo; 496,18 células/mm³ (± 133,48 células/mm³, IQR 367 células/mm³ e 596,5 células/mm³) aos 12 meses e 463,16 células/mm³ (±160,04 IQR 352 células/mm³) aos 18 meses de avaliação, respectivamente. Foi observada uma associação estatisticamente significativa entre os resultados da contagem de células CD4 (valor-p=0,009); tempo do paciente em tratamento anti-retroviral (valor-p=0,045); nível de adesão ao tratamento do MRC-19 e Cumprimento das Rotinas de Tratamento do HIV no Centro de Saúde de Moamba xii HIV (valor-p=0,01) e partilha ou sobras de medicamentos (valor-p=0.05) e o número de dias de atraso no levantamento de medicamentos. O medo de ser infectado pelo coronavírus (valor p=0,095) não influenciou os dias de atraso no levantamento de medicamentos. Outrossim, não foi encontrada nenhuma correlação entre atrasos no pagamento de medicamentos rendimento médio mensal (valor-p=0,85), apesar dos auto-relatos sobre a falta de dinheiro como condição para cumprir as rotinas de tratamento anti-retroviral. Conclusão: Os factores socioeconómicos e comportamentais foram mais importantes nas medidas tomadas para combater a COVID-19. No entanto, após a implementação das medidas de combate à COVID-19, o Centro de Saúde de Moamba melhorou a capacidades de tratamento de HIV com essas variações. Assim, o estudo recomenda a realização de estudos para explorar factores que promovam a cumprimento das rotinas de tratamento.

The Economically dependent countries with high HIV prevalence have been threatened by public health and administrative measures to control and contain the CVID/19 pandemic. Objective: The study investigates the impact of COVID-19-fighting restrictions on compliance with antiretroviral treatment routines among HIV-positive patients at Moamba Health Centre. Methods and Procedures: This is a quantitative and qualitative study with a retrospective descriptive component carried out through the analysis of clinical records of 20 participants in HIV care. It adopted semi-structured interviews to gather information (self-report) on factors affecting participants' compliance with ART routines (presence at consultations, compliance with the medication collection schedule) after the introduction of restrictive measures to fight COVID 19 in 20 patients followed on ART from October 2019 to March 2021.Statistical inference, in the form of parametric chi-square tests (X2), was used to assess associations and correlations between socioeconomic and biomedical variables extracted from clinical records (Summary Sheet). A reflective analysis of Braun and Clark was conducted using the information obtained from semi structured questionnaires (self-report). Results: Means of estimated adherence to HIV care ranged from 97% (±2.04, range of 92% and 100%) before the introduction of restrictive measures to fight COVID-19 to 94.39% (±3, 43% ranging between 86% and 98.9%) at the 12-month evaluation from April to September 2020. From October 2019 to March 2021, the average adherence rate was 96.6% (±2.72). The estimated average adherence during the study period was 96.22% (±3.38) and a median of 97.55% (IQR: 93.73% - 99.35%). During the study period, the average number of days late in collecting ARVs was 3.3 days (±1.72, IQR 2 ­ 4.75). It occurred between 6 months before and 12 months after COVID-19 combat measures (6 months before and 12 months after COVID-19 combat measures). From April to September 2020, the average of delays in collecting ARVs reached 1.6 days (±1.1 ± 1.1 IQR: 1-3) and decreased to 1.2 days (±0.89 IQR 1-3) during the third semester of evaluation from October 2020 to March 2021 showing that the measures to fight COVID-19 had a negative influence on the fulfilment of ART routines among the participants. The mean CD4 count during the study was 455.12 cells/mm3 (± 135.78, IQR: 345.3 cells/mm3 ­ 585.03 cells/mm3); 40% (8/20) of patients had CD4 ≤ 350 ≤ 350 cells/mm3 and 60% (12/20) had CD4 > 350 cells/mm3. CD4 averages varied from 72.8 cells/mm3 (± cells/mm3, IQR 342 cells/mm3 and 594 cells/mm3) after 6 months of study; 496.18 cells/mm3 (± 133.48 IQR 367 cells/mm3 ­ 596.5 cells/mm3) at 12 months of study and 463.16 cells/mm3 (±160.04 IQR 352 cells/mm3 ­ 555 cells/ mm3) at 18 months of the study, revealing that some of the measures to fight the COVID-19 strengthened the capacity for HIV/care provision at the Moamba Health Centre. Delays in fetching ARVs at the pharmacy influence CD4 results (p-value=0.009); time on ART (p-value=0.045); level of adherence to HIV care (p-value = 0.01) and sharing of ARV leftovers (p-value = 0.05). Fear of infection by Coronavirus (p-value=0.095) did not influence ARV retrieval delays. Self-reported about lack of money, as a condition for complying with ART routines, but not delays in collecting ARVs and mean monthly income (p-value=0.848). MRC-19 e Cumprimento das Rotinas de Tratamento do HIV no Centro de Saúde de Moamba xiv Conclusion: The results suggest that delays in fetching ARVs are not necessarily caused by financial constraints. It may be attributed to factors such as fear of infection by Coronavirus (although this did not influence significantly). However, fear of Coronavirus did affect people's willingness to access ARV services, even if it was not statistically significant. CD4 results, time on ART, the adherence level on HIV care, and sharing of ARV leftovers influenced the delays on ARVs collection. The study concludes that measures to fight COVID-19 increased the weight of socioeconomic and behavioural factors that affect adherence to HIV care and treatment routines, increasing delays in ARV collection. The effects of measures to fight COVID-19 highlighted the need to improve indicators, instruments, and procedures for recording, measuring, and evaluating factors affecting compliance with antiretroviral treatment routines, regarded as indicators of HIV care.

The Interplay Among HIV, LINE-1, and the Interferon Signaling System.

Human immunodeficiency viruses (HIVs) are retroviruses that replicate effectively in human CD4+ cells and cause the development of acquired immune deficiency syndrome (AIDS). On the other hand, type 1 long interspersed elements (LINE-1s or L1s) are the only active retroelements that can replicate autonomously in human cells. They, along with other active yet nonautonomous retroelements, have been associated with autoimmune diseases. There are many similarities between HIV and LINE-1. Being derived (or evolved) from ancient retroviruses, both HIV and LINE-1 replicate through a process termed reverse transcription, activate endogenous DNA and RNA sensors, trigger innate immune activation to promote interferon (IFN) expression, and are suppressed by protein products of interferon-stimulated genes (ISGs). However, these similarities make it difficult to decipher or even speculate the relationship between HIV and LINE-1, especially regarding the involvement of the IFN signaling system. In this review, we summarize previous findings on the relationships between HIV and innate immune activation as well as between LINE-1 and IFN upregulation. We also attempt to elucidate the interplay among HIV, LINE-1, and the IFN signaling system in hopes of guiding future research directions for viral suppression and immune regulation.

Sphingolipids: Effectors and Achilles Heals in Viral Infections?

As viruses are obligatory intracellular parasites, any step during their life cycle strictly depends on successful interaction with their particular host cells. In particular, their interaction with cellular membranes is of crucial importance for most steps in the viral replication cycle. Such interactions are initiated by uptake of viral particles and subsequent trafficking to intracellular compartments to access their replication compartments which provide a spatially confined environment concentrating viral and cellular components, and subsequently, employ cellular membranes for assembly and exit of viral progeny. The ability of viruses to actively modulate lipid composition such as sphingolipids (SLs) is essential for successful completion of the viral life cycle. In addition to their structural and biophysical properties of cellular membranes, some sphingolipid (SL) species are bioactive and as such, take part in cellular signaling processes involved in regulating viral replication. It is especially due to the progress made in tools to study accumulation and dynamics of SLs, which visualize their compartmentalization and identify interaction partners at a cellular level, as well as the availability of genetic knockout systems, that the role of particular SL species in the viral replication process can be analyzed and, most importantly, be explored as targets for therapeutic intervention.

Non-nucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy is associated with lower cell-associated HIV RNA and DNA levels compared to protease inhibitor-based therapy.

Background: It remains unclear whether combination antiretroviral therapy (ART) regimens differ in their ability to fully suppress human immunodeficiency virus (HIV) replication. Here, we report the results of two cross-sectional studies that compared levels of cell-associated (CA) HIV markers between individuals receiving suppressive ART containing either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI). Methods: CA HIV unspliced RNA and total HIV DNA were quantified in two cohorts (n = 100, n = 124) of individuals treated with triple ART regimens consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) plus either an NNRTI or a PI. To compare CA HIV RNA and DNA levels between the regimens, we built multivariable models adjusting for age, gender, current and nadir CD4+ count, plasma viral load zenith, duration of virological suppression, NRTI backbone composition, low-level plasma HIV RNA detectability, and electronically measured adherence to ART. Results: In both cohorts, levels of CA HIV RNA and DNA strongly correlated (rho = 0.70 and rho = 0.54) and both markers were lower in NNRTI-treated than in PI-treated individuals. In the multivariable analysis, CA RNA in both cohorts remained significantly reduced in NNRTI-treated individuals (padj = 0.02 in both cohorts), with a similar but weaker association between the ART regimen and total HIV DNA (padj = 0.048 and padj = 0.10). No differences in CA HIV RNA or DNA levels were observed between individual NNRTIs or individual PIs, but CA HIV RNA was lower in individuals treated with either nevirapine or efavirenz, compared to PI-treated individuals. Conclusions: All current classes of antiretroviral drugs only prevent infection of new cells but do not inhibit HIV RNA transcription in long-lived reservoir cells. Therefore, these differences in CA HIV RNA and DNA levels by treatment regimen suggest that NNRTIs are more potent in suppressing HIV residual replication than PIs, which may result in a smaller viral reservoir size. Funding: This work was supported by ZonMw (09120011910035) and FP7 Health (305522).

Who falls between the cracks? Identifying eligible PrEP users among people with Sub-Saharan African migration background living in Antwerp, Belgium.

INTRODUCTION: This study produces an estimate of the proportion of eligible PrEP users among people of Sub-Saharan African background based on the Belgian PrEP eligibility criteria and examines associations with socio-economic and demographic characteristics. METHODS: We performed logistic regression analysis on data of a representative community-based survey conducted among Sub-Saharan African communities (n = 685) living in Antwerp. RESULTS: Almost a third (30.3%) of the respondents were eligible to use PrEP. Those who were male, single, lower educated, undocumented, and had experienced forced sex were more likely to be eligible for PrEP use. The findings highlight the importance of taking intra-, interpersonal and structural HIV risk factors into account. CONCLUSIONS: The study shows high unmet PrEP needs in this population, especially among those with high vulnerability for HIV acquisition. A better understanding of barriers to PrEP use in this population group is needed to allow for equitable access.

Hypoactivation in the precuneus and posterior cingulate cortex during ambiguous decision making in individuals with HIV.

People with human immunodeficiency virus (HIV) often have neurocognitive impairment. People with HIV make riskier decisions when the outcome probabilities are known, and have abnormal neural architecture underlying risky decision making. However, ambiguous decision making, when the outcome probabilities are unknown, is more common in daily life, but the neural architecture underlying ambiguous decision making in people with HIV is unknown. Eighteen people with HIV and 20 controls completed a decision making task while undergoing functional magnetic resonance imaging scanning. Participants chose between a certain reward and uncertain reward with a known (risky) or unknown (ambiguous) probability of winning. There were three levels of risk: high, medium, and low. Ambiguous > risky brain activity was compared between groups. Ambiguous > risky brain activity was correlated with emotional/psychiatric functioning in people with HIV. Both groups were similarly ambiguity-averse. People with HIV were more risk-averse than controls and chose the high-risk uncertain option less often. People with HIV had hypoactivity in the precuneus, posterior cingulate cortex (PCC), and fusiform gyrus during ambiguous > medium risk decision making. Ambiguous > medium risk brain activity was negatively correlated with emotional/psychiatric functioning in individuals with HIV. To make ambiguous decisions, people with HIV underrecruit key regions of the default mode network, which are thought to integrate internally and externally derived information to come to a decision. These regions and related cognitive processes may be candidates for interventions to improve decision-making outcomes in people with HIV.

Trends in knowledge of HIV status and efficiency of HIV testing services in sub-Saharan Africa, 2000-20: a modelling study using survey and HIV testing programme data.

BACKGROUND: Monitoring knowledge of HIV status among people living with HIV is essential for an effective national HIV response. This study estimates progress and gaps in reaching the UNAIDS 2020 target of 90% knowledge of status, and the efficiency of HIV testing services in sub-Saharan Africa, where two thirds of all people living with HIV reside. METHODS: For this modelling study, we used data from 183 population-based surveys (including more than 2·7 million participants) and national HIV testing programme reports (315 country-years) from 40 countries in sub-Saharan Africa as inputs into a mathematical model to examine trends in knowledge of status among people living with HIV, median time from HIV infection to diagnosis, HIV testing positivity, and proportion of new diagnoses among all positive tests, adjusting for retesting. We included data from 2000 to 2019, and projected results to 2020. FINDINGS: Across sub-Saharan Africa, knowledge of status steadily increased from 5·7% (95% credible interval [CrI] 4·6-7·0) in 2000 to 84% (82-86) in 2020. 12 countries and one region, southern Africa, reached the 90% target. In 2020, knowledge of status was lower among men (79%, 95% CrI 76-81) than women (87%, 85-89) across sub-Saharan Africa. People living with HIV aged 15-24 years were the least likely to know their status (65%, 62-69), but the largest gap in terms of absolute numbers was among men aged 35-49 years, with 701 000 (95% CrI 611 000-788 000) remaining undiagnosed. As knowledge of status increased from 2000 to 2020, the median time to diagnosis decreased from 9·6 years (9·1-10) to 2·6 years (1·8-3·5), HIV testing positivity declined from 9·0% (7·7-10) to 2·8% (2·1-3·9), and the proportion of first-time diagnoses among all positive tests dropped from 89% (77-96) to 42% (30-55). INTERPRETATION: On the path towards the next UNAIDS target of 95% diagnostic coverage by 2025, and in a context of declining positivity and yield of first-time diagnoses, disparities in knowledge of status must be addressed. Increasing knowledge of status and treatment coverage among older men could be crucial to reducing HIV incidence among women in sub-Saharan Africa, and by extension, reducing mother-to-child transmission. FUNDING: Steinberg Fund for Interdisciplinary Global Health Research (McGill University); Canadian Institutes of Health Research; Bill & Melinda Gates Foundation; Fonds the recherche du Québec-Santé; UNAIDS; UK Medical Research Council; MRC Centre for Global Infectious Disease Analysis; UK Foreign, Commonwealth & Development Office.

Treatment success for patients with tuberculosis receiving care in areas severely affected by Hurricane Matthew - Haiti, 2016.

BACKGROUND: On October 4, 2016, Hurricane Matthew struck southwest Haiti as a category 4 storm. The goal of this study was to evaluate the impact of the hurricane on tuberculosis (TB) services and patient outcomes in the three severely affected departments-Sud, Grand'Anse, and Nippes-of southwest Haiti. METHODS: We developed a standard questionnaire to assess a convenience sample of health facilities in the affected areas, a patient tracking form, and a line list for tracking all patients with drug-susceptible TB registered in care six months before the hurricane. We analyzed data from the national TB electronic surveillance system to determine outcomes for all patients receiving anti-TB treatment in the affected areas. We used logistic regression analysis to determine factors associated with treatment success. RESULTS: Of the 66 health facilities in the three affected departments, we assessed 31, accounting for 536 (45.7%) of 1,174 TB patients registered in care when Hurricane Matthew made landfall in Haiti. Three (9.7%) health facilities sustained moderate to severe damage, whereas 18 (58.1%) were closed for <1 week, and five (16.1%) for ≥1 week. Four weeks after the hurricane, 398 (73.1%) of the 536 patients in the assessed facilities were located. Treatment success in the affected departments one year after the hurricane was 81.4%. Receiving care outside the municipality of residence (adjusted odds ratio [aOR]: 0.46, 95% confidence interval [CI]: 0.27-0.80) and HIV positivity (aOR: 0.31, 95% CI: 0.19-0.51) or unknown HIV status (aOR: 0.49, 95% CI: 0.33-0.74) were associated with significantly lower rates of treatment success. CONCLUSIONS: Despite major challenges, a high percentage of patients receiving anti-TB treatment before the hurricane were located and successfully treated in southwest Haiti. The lessons learned and results presented here may help inform policies and guidelines in similar settings for effective TB control after a natural disaster.

Stigma reduction: an essential ingredient to ending AIDS by 2030.

Ending the AIDS epidemic by 2030 will require addressing stigma more systematically and at a larger scale than current efforts. Existing global evidence shows that stigma is a barrier to achieving each of the 90-90-90 targets; it undermines HIV testing, linkage to care, treatment adherence, and viral load suppression. However, findings from both research studies and programmatic experience have helped to inform the growing body of knowledge regarding how to reduce stigma, leading to key principles for HIV stigma reduction. These principles include immediately addressing actionable drivers of stigma, centring groups affected by stigma at the core of the response, and engaging opinion leaders and building partnerships between affected groups and opinion leaders. Although there is still room to strengthen research on stigma measurement and reduction, in particular for intersectional stigma, the proliferation of evidence over the past several decades on how to measure and address stigma provides a solid foundation for immediate and comprehensive action.

Association of rs12722 COL5A1 with pulmonary tuberculosis: a preliminary case-control study in a Kazakhstani population.

Lung cavitation is the classic hallmark of TB, which facilitates the disease development and transmission. It involves the degradation of lung parenchyma which is mainly made up of collagen fibers by metalloproteinases (MMPs) produced by activated monocyte-derived cells, neutrophils and stromal cells. The following population-based preliminary case-control study of adults with TB (50) and controls (112) without TB was used to investigate possible association between rs1800012 in COL1A1, rs12722 in COL5A1 genes and pulmonary TB in Kazakhstan. We examined 162 samples (50 cases and 112 controls) to study the associations between TB disease status and demographic variables along with single nucleotide polymorphisms related to COLA1 and COL5A1. The unadjusted χ2 and multivariable logistic regression was performed to find out relationships between SNP and other predictors. Preliminary findings suggest that there is a statistically significant association of age (AOR = 0.97, 95% CI:0.94-0.99, p value = 0.049), social status (AOR = 2.41, 95% CI:1.16-5.02, p value = 0.018), HIV status (AOR = 7.12, 95% CI:1.90-26.7, p value = 0.004) and heterozygous rs12722 SNP (AOR = 2.47, 95% CI:1.17-5.19, p value = 0.018) polymorphism of COL5A1 gene with TB susceptibility. The association of collagen genes with TB pathogenesis indicates that anti TB programs can include development of new drug regimens that include MMP inhibitors which has been found to be helpful in collagen remodeling and repair. Therapeutic targeting of MMPs will prevent extracellular matrix and collagen degradation and granuloma maturation.

Longitudinal Dynamics of Intact HIV Proviral DNA and Outgrowth Virus Frequencies in a Cohort of Individuals Receiving Antiretroviral Therapy.

BACKGROUND: The replication-competent human immunodeficiency virus (HIV) reservoir is the major barrier to cure. The quantitative viral outgrowth assay (QVOA), the gold-standard method to quantify replication-competent HIV, is resource intensive, which limits its application in large clinical trials. The intact proviral DNA assay (IPDA) requires minimal cell input relative to QVOA and quantifies both defective and intact proviral HIV DNA, the latter potentially serving as a surrogate marker for replication-competent provirus. However, there are limited cross-sectional and longitudinal data on the relationship between IPDA and QVOA measurements. METHODS: QVOA and IPDA measurements were performed on 156 resting CD4 T-cell (rCD4) samples from 83 antiretroviral therapy-suppressed HIV-positive participants. Longitudinal QVOA and IPDA measurements were performed on rCD4 from 29 of these participants. RESULTS: Frequencies of intact, defective, and total proviruses were positively associated with frequencies of replication-competent HIV. Longitudinally, decreases in intact proviral frequencies were strikingly similar to that of replication-competent virus in most participants. In contrast, defective proviral DNA frequencies appeared relatively stable over time in most individuals. CONCLUSIONS: Changes in frequencies of IPDA-derived intact proviral DNA and replication-competent HIV measured by QVOA are similar. IPDA is a promising high-throughput approach to estimate changes in the frequency of the replication-competent reservoir.

HIV/SARS-CoV-2 coinfection: A global perspective.

Since its first appearance in Wuhan, China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread throughout the world and has become a global pandemic. Several medical comorbidities have been identified as risk factors for coronavirus disease 2019 (COVID-19). However, it remains unclear whether people living with human immunodefeciency virus (PLWH) are at an increased risk of COVID-19 and severe disease manifestation, with controversial suggestion that HIV-infected individuals could be protected from severe COVID-19 by means of antiretroviral therapy or HIV-related immunosuppression. Several cases of coinfection with HIV and SARS-CoV-2 have been reported from different parts of the globe. This review seeks to provide a holistic overview of SARS-CoV-2 infection in PLWH.

Plano estrategico Multissectorial de prevenção e controlo de doenças não transmissíveis / Multisectoral strategic plan for the prevention and control of non-communicable diseases

A morte prematura por Doenças Não Transmissíveis (DNTs), continua a ser um dos principais desafios para o desenvolvimento a nível global, ceifando por ano perto de 15 milhões de vidas em idades compreendidas entre 30 e 70 anos. Moçambique não permanece inócuo pois já é notável a transição epidemiológica com o duplo peso das doenças transmissíveis e não transmissíveis. Em África o peso das Doenças Cardiovasculares, Diabetes Mellitus, Doenças Respiratórias Crónicas e o Cancro tem estado a aumentar de forma desproporcional entre os países de baixa e média renda, afetando sobretudo os grupos populacionais mais pobres e vulneráveis, impulsionado por factores como a pobreza, a globalização do mercado, o comércio de produtos prejudiciais à saúde, a crescente urbanização, crescimento e envelhecimento da população. Em Moçambique, à semelhança de muitos países, o desenvolvimento económico está a trazer grandes benefícios, mas também mudanças negativas na dieta e estilos de vida. É estimado que cerca de um terço das mortes no país sejam causadas pelas DNTs, e o risco de mortalidade prematura, ou seja, o risco de morte por DNTs antes dos 70 anos de idade, é de 18%. Este facto é preocupante pois maioria destas mortes prematuras e incapacidade por DNTs, pode ser evitada ou adiada através da redução da exposição aos factores de risco como consumo excessivo de álcool, consumo do tabaco, dieta não saudável e inatividade física.

The Effect of Antiretroviral Therapy on IL-6, IL-1ß, TNF-α, IFN-γ Levels and their Relationship with HIV-RNA and CD4+ T Cells in HIV Patients.

BACKGROUND: Serum cytokine levels over the course of HIV infection usually increase with immunosuppression and decrease after antiretroviral treatment (ART). OBJECTIVES: The aim of the study is to compare cytokine levels between HIV-infected patients (HIP) and controls and investigate the relationship between CD4+T cell count, HIV-RNA levels, and cytokine levels. METHODS: The study subjects comprised ART-naive HIP (n=30) with no comorbidities and age-and sex-matched healthy controls. We measured levels of IL-6, IL-1ß, TNF-α, and IFN-γ in serum samples of HIP at the beginning and at month 6 of ART and in controls. RESULTS: The mean age of the study subjects was 38.7 ±10.3 years, with men making up 86.7% of the study subjects (n=26). IL-6, IL-1ß, and TNF-α levels were significantly higher in both ART-naive (p<0.001, p=0.002, p=0.001) and ART-experienced HIP (p<0.001) than controls. The IFN-γ level was lower in both ART-naive and ART-experienced HIP compared to controls (p=0.082 and p=0.002). There was a positive correlation between the CD4+T cell count and serum concentration of IFN- γ(r=0.320, p<0.05). While the serum IFN-γ concentration showed a negative correlation with the HIVRNA level(r=-0.412, p<0.001), the serum IL-1ß, IL-6, and TNF-α concentrations showed a positive correlation with the HIV-RNA level (r=0.349, p<0.001; r:0.54, p<0.001; r:0.438, p<0.00). CONCLUSION: Although serum concentrations of IL-6, IL-1ß and TNF-α showed a significant decrease after ART, they were still significantly higher than the controls. IFN-γ responded differently to ART compared to the other cytokines, indicating that it may play a distinct and important role in the pathogenesis of HIV infection.

Case report: one case of coronavirus disease 2019 (COVID-19) in a patient co-infected by HIV with a normal CD4+ T cell count.

BACKGROUND: The COVID-19 has been a severe pandemic all around the world. Nowadays the patient with co-infection of HIV and SARS-CoV-2 was rarely reported. Here we reported a special case with HIV and SARS-CoV-2 co-infection, which showed a prolonged viral shedding duration. CASE PRESENTATION: The patient was infected with HIV 8 years ago through sexual transmission and had the normal CD4+T cell count. She was found SARS-CoV-2 positive using real-time Polymerase Chain Reaction (RT-PCR) during the epidemic. Most importantly, the patient had a prolonged viral shedding duration of SARS-CoV-2 about 28 days. CONCLUSION: The viral shedding duration may be prolonged in people living with HIV. The 14 days isolation strategy might not be long enough for them. The isolation or discharge of these patients needs further confirmation for preventing epidemics.

Bone Marrow Culture Yield for the Diagnosis of Opportunistic Diseases in Patients with AIDS and Disseminated Kaposi Sarcoma.

BACKGROUND: Disseminated Kaposi sarcoma (DKS) is present in patients with advanced HIV infection in whom co-infection with other opportunistic pathogens can occur. Bone marrow (BM) aspirate and biopsy comprise a robust diagnostic tool in patients with fever, cytopenias, and abnormal liver tests. However, the yield in patients with DKS has not been determined. OBJECTIVE: The aim of this study was to evaluate the utility of BM aspirate and biopsy in patients with DKS. METHODS: We included 40 male patients with a recent diagnosis of DKS. BM aspirate and biopsy was performed as part of the workup to rule out co-infections. RESULTS: In four patients, Mycobacterium avium complex (MAC) was recovered from culture. In other four patients, intracellular yeasts were observed in the Grocott stain, diagnosed as Histoplasma. The yield of BM was calculated in 20%. Only 12 patients (30%) had fever and 11 (27.5%) had pancytopenia. Alkaline phosphatase (ALP) above normal values and C-reactive protein (CRP) were higher in patients with positive results for BM than in those with negative results (63% vs. 21.9%, and 3.0 vs. 1.2 mg/L; p = 0.03 in both comparisons). No differences were found when complete blood-count abnormalities were compared. CONCLUSION: We recommend performing a BM aspirate for stains, culture, and biopsy in all HIV patients with DKS, as this will permit the early diagnosis of co-infections and prevent further complications in those who receive chemotherapy.